Effective strategies for promoting healthy brain aging and preventing Alzheimer's disease (AD) are increasingly important given the growth of the elderly population and the resulting increase in the incidence of AD. Accumulating evidence suggests that exercise and cardiorespiratory (CR) fitness may protect against cognitive decline and age-related brain changes in non-demented aging. CR fitness has not been studied in the early stages of AD. Neuroimaging surrogate measures of brain aging and brain disease are increasingly used lo detect disease associations, explore causal mechanisms, and establish an intervention's disease-modifying effect. Thus, our long-term goal is to investigate CR fitness in AD and its relationship to structural brain changes associated with early-stage AD and non-demented aging. Our overall hypothesis is that increased CR fitness will be inversely associated with neuroimaging markers of brain aging. We will assess maximal oxygen consumption (VO2 max), the gold-standard measure of CR fitness, in a cohort (n = 64) of non-demented controls and early-stage AD subjects completing clinical and neuroimaging assessments as part of the University of Kansas (KU) Brain Aging Project. Brain aging markers include MRI measures of whole brain atrophy, hippocampal atrophy, white matter lesions, and infarcts. We will test our hypothesis with three specific aims. Aim 1: Assess for group differences in CR fitness in a cohort of non-demented controls and early-stage AD participants. Aim 2: Evaluate the relationship of CR fitness and hippocampal volume in non-demented aging and early-stage AD. Aim 3: Assess CR fitness in relation to MRI markers of brain aging: atrophy, white matter lesions, and infarcts. This preliminary, multidisciplinary study will generate cross-sectional pilot data assessing the relation between CR fitness, brain aging and AD-related brain injury. Utilizing well-characterized subjects with clinical and neuroimaging assessments through the KU Brain Aging Project enables this project to be feasible in a discrete time-frame. Exercise is already a key prevention strategy for health issues beyond preventing brain aging and cognitive decline. Despite this, an estimated 40-50 million adults in the US do not currently obtain the recommended amount of physical activity. A clear demonstration of the beneficial effects of exercise on brain aging and AD would be important for public health policy and effective for encouraging the public to adapt more active lifestyles. If our hypotheses are correct, we would pursue longitudinal interventional studies to better establish causality and assess increasing CR fitness as a way to promote healthy brain aging and moderate AD-related brain changes. [unreadable] [unreadable]